The Role of Sphingosine-1-Phosphate Receptor 2 in Mouse Retina Light Responses
Abhishek P. Shrestha,
Megan Stiles,
Richard C. Grambergs,
Johane M. Boff,
Saivikram Madireddy,
Koushik Mondal,
Rhea Rajmanna,
Hunter Porter,
David M. Sherry,
Richard L. Proia,
Thirumalini Vaithianathan,
Nawajes Mandal
Affiliations
Abhishek P. Shrestha
Department of Pharmacology, Addiction Science, and Toxicology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Megan Stiles
Departments of Cell Biology, Neurosurgery, and Pharmacological Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Richard C. Grambergs
Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Johane M. Boff
Department of Pharmacology, Addiction Science, and Toxicology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Saivikram Madireddy
College of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163, USA
Koushik Mondal
Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Rhea Rajmanna
Department of Pharmacology, Addiction Science, and Toxicology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Hunter Porter
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
David M. Sherry
Departments of Cell Biology, Neurosurgery, and Pharmacological Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
Richard L. Proia
Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Thirumalini Vaithianathan
Department of Pharmacology, Addiction Science, and Toxicology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Nawajes Mandal
Department of Ophthalmology, Hamilton Eye Institute, University of Tennessee Health Science Center, Memphis, TN 38163, USA
The bioactive sphingolipid sphingosine-1-phosphate (S1P) acts as a ligand for a family of G protein-coupled S1P receptors (S1PR1-5) to participate in a variety of signaling pathways. However, their specific roles in the neural retina remain unclear. We previously showed that S1P receptor subtype 2 (S1PR2) is expressed in murine retinas, primarily in photoreceptors and bipolar cells, and its expression is altered by retinal stress. This study aims to elucidate the role of S1PR2 in the mouse retina. We examined light responses by electroretinography (ERG), structural differences by optical coherence tomography (OCT), and protein levels by immunohistochemistry (IHC) in wild-type (WT) and S1PR2 knockout (KO) mice at various ages between 3 and 6 months. We found that a- and b-wave responses significantly increased at flash intensities between 400~2000 and 4~2000 cd.s/m2, respectively, in S1PR2 KO mice relative to those of WT controls at baseline. S1PR2 KO mice also exhibited significantly increased retinal nerve fiber layer (RNFL) and outer plexiform layer (OPL) thickness by OCT relative to the WT. Finally, in S1PR2 KO mice, we observed differential labeling of synaptic markers by immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (RT-qPCR). These results suggest a specific involvement of S1PR2 in the structure and synaptic organization of the retina and a potential role in light-mediated functioning of the retina.
